WO2019015439A1 - Dispositif d'imagerie spectrale rapide de molécule tissulaire - Google Patents

Dispositif d'imagerie spectrale rapide de molécule tissulaire Download PDF

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Publication number
WO2019015439A1
WO2019015439A1 PCT/CN2018/091980 CN2018091980W WO2019015439A1 WO 2019015439 A1 WO2019015439 A1 WO 2019015439A1 CN 2018091980 W CN2018091980 W CN 2018091980W WO 2019015439 A1 WO2019015439 A1 WO 2019015439A1
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WIPO (PCT)
Prior art keywords
unit
sample
detecting unit
fluorescence
line
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PCT/CN2018/091980
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English (en)
Chinese (zh)
Inventor
王强
邵金华
孙锦
段后利
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无锡海斯凯尔医学技术有限公司
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Publication of WO2019015439A1 publication Critical patent/WO2019015439A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00131—Accessories for endoscopes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00163—Optical arrangements
    • A61B1/00165—Optical arrangements with light-conductive means, e.g. fibre optics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/043—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters

Definitions

  • the present invention relates to the field of medical devices, and more particularly to a rapid tissue molecular spectral imaging device.
  • Tumors are major diseases that pose a serious threat to human health. Numerous studies have shown that more than 90% of tumors are derived from epithelial cell lesions, and molecular and cellular levels of variation occur during cancer development. Fiber-optic beam-based high-resolution optical endoscopic imaging technology that achieves micron or sub-micron resolution, enabling endoscopic magnification up to 1000 times, and is lossless compared to other medical imaging techniques (such as CT, MRI, PET, etc.) Real-time, in-vivo detection of micro-neoplastic lesions and other technical advantages can better improve the early diagnosis rate of tumors.
  • the probe end of the endoscopic imaging can be deeply penetrated into the living body to complete the real-time non-destructive testing of the micro-scale in vivo, and realize the “in-vivo biopsy” without sampling, which brings new technical means for early detection of molecular molecular lesions.
  • the present invention has been made in consideration of the above problems.
  • the present invention provides a rapid tissue molecular spectroscopic imaging apparatus comprising a light emitting unit, a steering unit, a scanning unit and a spectral detecting unit, wherein the light emitting unit is for emitting a line beam; the steering unit is for steering the line a beam of light passing through the sample; the scanning unit is for adjusting the direction of the redirected line beam to scan the sample line by line; and the spectral detection unit is configured to acquire the fluorescence and form a spatial image and spectral information of the sample .
  • the steering unit is a dichroic mirror.
  • the scanning unit is a single scanning galvanometer, or a spatial light modulator.
  • the apparatus further includes a relay unit and an endoscope unit disposed downstream of the scanning unit, wherein the relay unit is configured to focus a line beam scanned by the scanning unit to the endoscopic unit
  • the endoscope unit is configured to conduct and focus the focused line beam onto the sample and receive fluorescence emitted by the sample; the fluorescence is passed by the relay unit, the scanning unit, and the steering unit Spectral detection unit acquisition.
  • the detecting unit further includes a first focusing lens disposed between the line array detecting unit and the switching control unit for focusing the fluorescence emitted by the sample to the The line array detection unit.
  • the detecting unit further includes a slit and/or a filter disposed downstream of the second focusing lens, wherein: the slit is for allowing only fluorescence of a focus plane to pass; and the filtering It is used to filter out stray light.
  • FIG. 1 shows a schematic block diagram of a rapid tissue molecular spectroscopic imaging apparatus in accordance with one embodiment of the present invention
  • the fluorescence returned along the same optical path as the line beam is transmitted almost entirely through the steering unit 120 and is conducted to the detecting unit 160.
  • the steering unit 120 that satisfies the above conditions may be a dichroic mirror.
  • the dichroic mirror may have a wavelength in the wavelength range of 40 nm to 2200 nm.
  • the line beam combining detection unit 160 can image line by line, so the imaging speed is greatly improved compared to the existing point-by-point imaging.
  • the scanning unit 130 may be a single scanning galvanometer.
  • the frequency of the scanning galvanometer can be in the frequency range of 10-2000 kHz.
  • the use of a single scanning galvanometer can greatly reduce noise, and the complexity of the composition and control of the device improves the stability of the whole machine while reducing manufacturing costs and maintenance costs.
  • the scanning unit 130 can also be a spatial light modulator. Spatial light modulators are relatively expensive compared to scanning galvanometers.
  • the fast tissue molecular spectral imaging apparatus 100 further includes a relay unit 140 and an endoscope unit 150 disposed downstream of the scanning unit 130.
  • 2-3 illustrate optical path diagrams and block diagrams of a fast tissue molecular spectral imaging apparatus 200 in accordance with an embodiment of the present invention.
  • the same or similar components in Fig. 2-3 as in Fig. 1 are given the same reference numerals.
  • a specific implementation of the relay unit 140, the endoscopic unit 150, and the detecting unit 160 in accordance with a specific embodiment of the present invention will be described in detail below with reference to FIGS. 2-3.
  • the endoscope unit 150 is configured to conduct and focus the line beam focused by the relay unit 140 onto the sample and receive the fluorescence emitted by the sample.
  • the fluorescence is collected by the detection unit 160 via the relay unit 140 and the steering unit 120.
  • the endoscope unit 150 can include a coupling objective 152, a miniature objective 156, and an imaging fiber bundle 154 coupled between the coupling objective 152 and the micro objective 156.
  • the relay unit 140 may include two relay lenses L4, L5 that cooperate to relay the scanned line beam to the rear pupil of the coupling objective 152 in the endoscope unit 150.
  • the coupling objective 152 is used to couple (e.g., focus) the line beam into the proximal end of the imaging fiber bundle 154 (near the operator's end).
  • the imaging fiber bundle 154 is used to conduct a line beam to the distal end of the imaging fiber bundle 154 (away from the end of the operator).
  • the miniature objective lens 156 is used to focus the laser light conducted by the imaging fiber bundle 154 onto the detection surface of the sample.
  • the detection surface can be located at a desired depth below the surface of the sample.
  • the fluorophore at the detection face of the sample is excited to fluoresce.
  • the fluorescent signal is collected by the miniature objective lens 156, transmitted through the imaging fiber bundle 154, the coupling objective lens 152, and the relay unit 140, and the scanning unit 130 reflects and passes through the steering unit 120 to enter the detecting unit 160.
  • the number of bundles of light included in the imaging fiber bundle 154 can be greater than ten.
  • the miniature objective lens 156 is not required.
  • the micro objective lens 156 may alternatively be omitted.
  • the micro objective lens 156 can be designed to extend into the digestive tract, the respiratory tract, and the like, and is in contact with the surface of the digestive tract, the respiratory tract, and the like.
  • the detecting unit 160 collects fluorescence returned through the endoscope unit 150, the relay unit 140, the scanning unit 130, and the steering unit 120 in sequence, and forms a spatial image and spectral information of the sample.
  • the spatial image of the sample includes a two-dimensional image of the detection surface of the sample.
  • the spectral information includes the energy distribution of the fluorescence generated by the sample stimulated at different wavelengths to aid in the acquisition of tissue information (eg, for analysis of tumors).
  • the detection unit 160 can include a line array detection unit 162, a spectral detection unit 164, and a switching control unit 166, as shown in Figures 2-3.
  • the spectral detection unit 164 is used to acquire fluorescence and form spectral information of the sample, which will be described in detail later.
  • the switching control unit 166 is configured to perform switching selection between the line array detecting unit 162 and the spectrum detecting unit 164 to selectively acquire spatial image or spectral information.
  • the switching control unit 166 selectively switches the transmission path of the fluorescence, for example, to cause the fluorescence to enter the line array detecting unit 162 or the spectrum detecting unit 164.
  • the switching control unit 166 can be a mirror, a digital micromirror device (DMD), or a spatial light modulator.
  • the digital micromirror device can realize the projection or reflection of the optical path by controlling the on and off.
  • An embodiment using a digital micromirror device as the switching control unit 166 is schematically illustrated in FIG.
  • the switching control unit 166 is turned on to transmit fluorescence, and the linear array detecting unit 162 performs spatial imaging to find a target area (for example, a tumor); then, when it is desired to perform specific analysis on the target area, the switching control unit is controlled.
  • the 166 is blocked, the fluorescence is reflected to the spectrum detecting unit 164, and the spectral information of the target region is acquired by the spectrum detecting unit 164.
  • the switching control unit 166 employs a mirror or a spatial light modulator, those skilled in the art can modify the optical path in accordance with the principles disclosed herein.
  • spectral detection unit 164 is a spectroscopic camera.
  • Spectral cameras can be any type of spectroscopic camera that may or may not be present in the future, such as the Pika L-spectrum camera from RESONON, USA, and the FX10 spectrum from Specim, Finland.
  • a camera or the like can form spectral information of a sample based on the collected fluorescence.
  • the detecting unit 160 further includes a second focusing lens L7 disposed between the spectrum detecting unit 164 and the switching control unit 166, as shown in FIG. 3, for focusing the fluorescence emitted by the sample to the spectrum.
  • the detection unit 164 is to obtain more reliable spectral information.
  • the spectral detection unit 164 can include prism-grating-prisms (PGP prisms) 164a, converging lenses 164b, and faces disposed in sequence.
  • Array detector 164c When switching to the spectral function by the switching control unit 166, the PGP prism 164a is used to perform dispersion splitting of the fluorescence transmitted by the steering unit 120.
  • Converging lens 164b is used to focus the dispersion-separated fluorescence onto the photosensitive surface of area array camera 166.
  • the number of converging lenses 164b is related to the number of channels of the obtained spectrum, that is, more spectral images of more channels are desired, and more converging lenses are used.
  • the area array detector 164c is used to form spectral information of the sample.
  • the area array detector 166 may be various types of area array cameras such as a CCD (Charge Coupled Device) area array camera or a CMOS (Complementary Metal Oxide Semiconductor) area array camera.
  • the detecting optical path 160 preferably further includes a second focusing lens L7 and a collimating lens L8 between the switching control unit 166 and the spectrum detecting unit 164 along the optical path direction. Set them in sequence, as shown in Figure 4-5.
  • the second focus lens L7 is used to focus the fluorescence emitted by the sample.
  • the focused line beam illuminates the fluorescence emitted by the sample to be received.
  • the detecting unit 160 Through the steering and scanning of the scanning unit 130, the fluorescence emitted by all the rows of the sample is finally received by the detecting unit 160, and arranged into spectral cube data according to the scanning trajectory, and further Quickly obtain spectral information of the tissue.
  • a collimating lens L8 is used to collimate the focused fluorescence.
  • a slit (not shown) may be provided between the second focus lens L7 and the collimator lens L8 for allowing only the fluorescence of the focus plane to pass.
  • the size of the slit may range from several tens of nanometers to several tens of millimeters. The presence of the slits causes stray light outside the focus plane to be blocked.
  • the detecting unit 160 may further include a filter.
  • a filter (not shown) is disposed downstream of the second focus lens L7, that is, between the second focus lens L7 and the collimator lens L8 for filtering out stray light. In the embodiment having a slit, a filter may be disposed between the second focus lens L7 and the slit.
  • the fast tissue molecular spectroscopic imaging apparatus 100 uses a line source to excite the sample, scans the line beam with a one-dimensional scanning unit 130 (for example, a single scanning galvanometer), and uses the detecting unit 160 to detect the sample excitation light in a one-dimensional direction. Achieve confocal. Since the linear beam and the detecting unit 160 are combined to obtain the spatial image and spectral information of the tissue molecule, the imaging speed of the tissue molecule can be greatly improved, real-time imaging can be realized, and the tissue condition can be assisted by spectral information (for example, for tumor). analysis). Since the scanning unit 130 performs only one-dimensional scanning, the stability of the system can be effectively improved.
  • a one-dimensional scanning unit 130 for example, a single scanning galvanometer

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
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  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

La présente invention concerne un dispositif d'imagerie spectrale rapide d'une molécule tissulaire, comprenant : une unité d'émission de lumière ; une unité de déviation ; une unité de balayage ; et une unité de détection. L'unité d'émission de lumière est utilisée pour émettre un faisceau de lumière linéaire. L'unité de déviation est utilisée pour dévier le faisceau de lumière linéaire et permet que la lumière fluorescente émise par un échantillon traverse celle-ci. L'unité de balayage est utilisée pour ajuster une direction du faisceau de lumière linéaire dévié pour balayer l'échantillon ligne par ligne. L'unité de détection est utilisée pour collecter la lumière fluorescente et former une image spatiale et des informations spectrales de l'échantillon. Un faisceau de lumière linéaire et une unité de détection de spectre sont utilisés en combinaison pour obtenir une image spatiale et des informations spectrales d'une molécule tissulaire, de sorte qu'une vitesse d'imagerie de la molécule tissulaire soit significativement augmentée, une imagerie en temps réel peut être réalisée, et les informations spectrales peuvent être utilisées pour faciliter une analyse tissulaire (par exemple, une analyse de tumeur). Étant donné que l'unité de balayage effectue seulement un balayage unidimensionnel, la stabilité du système peut être efficacement augmentée.
PCT/CN2018/091980 2017-07-20 2018-06-20 Dispositif d'imagerie spectrale rapide de molécule tissulaire WO2019015439A1 (fr)

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CN107361725B (zh) * 2017-07-20 2024-02-27 无锡海斯凯尔医学技术有限公司 快速组织分子成像装置
CN107361723B (zh) * 2017-07-20 2024-02-13 无锡海斯凯尔医学技术有限公司 快速组织分子光谱成像装置

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EP1291627A1 (fr) * 2001-09-06 2003-03-12 Europhoton Gesellschaft mbH für Optische Sensorik Procédé et arrangement pour l'acquisition multiparamétrique de photons individuels pour la production simultanée de fluorescence résolues temporellement et spatialement ainsi que temporellement et spectralement
CN1605856A (zh) * 2004-11-18 2005-04-13 上海交通大学 激光荧光关联谱单分子分析仪
CN101904737A (zh) * 2010-08-09 2010-12-08 华中科技大学 活体荧光内窥光谱成像装置
CN102507001A (zh) * 2011-10-18 2012-06-20 中国科学院上海技术物理研究所 基于棱镜-光栅-棱镜分光的折反式成像光谱仪光学系统
CN104597590A (zh) * 2014-12-30 2015-05-06 深圳先进技术研究院 一种超分辨荧光光谱成像显微镜
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